Background: The obesity paradox has been described in several cohort studies. However, evidence of intentionality of weight loss on all-cause mortality and major cardiovascular events (MACE) in prospective cohorts is not clear. Aim: To summarize and evaluate the observational evidence of the effects of intentionality of weight loss on MACE and all-cause mortality. Methods: Through a systematic review, multiple electronic databases (MEDLINE/PubMed, Web of Science, SciELO and LILACS) were searched and manual search for studies published up to September 2016 was performed. Cohort studies that reported intentionality (intentional and unintentional) weight loss compared to no weight change with risk estimates for MACE and mortality in primary prevention cohorts were included. A pre-defined protocol in accordance with the standards of quality for reporting meta-analysis of observational studies (MOOSE guidelines) was used. Random effects were used to summarize effects and heterogeneity was analyzed with I2. Subgroups were analyzed by age (> 65) and comorbidities reported during follow-up. Results: Our search found 22.008 references and 13 studies met the selection criteria and were involved in the meta-analysis, including 142346 participants (51,3% men, age ranging from 42.2 to 75.3 years). Thirteen studies (25522 participants) reported intentional weight loss and 12 studies (25107 participants) reported non-intentional weight loss. Time of follow-up varied from 2 to 20 years. For intentional weight loss RR (95% CI) were 0.99 (0.92; 1.07) (I2 = 58.2%, p=0.003) and 1.03 (0.9; 1.15) (I2 = 0.0%, p=0.995) for all-cause and MACE, respectively. Subgroups by age of cohort and comorbidities did not change the estimates materially. For unintentional weight loss, RR (95% CI) were 1.25 (1.17; 1.34) (I2 = 70.4%, p=0.000) and 1.09 (0.96; 1.23) (I2 = 78.3%, p=0.001) for all-cause mortality and MACE, respectively. Subgroup analysis for participants with comorbidities yielded RR (95% CI) of 1.44 (1.31; 1.56) (I2 = 59.1%, p=0.012) and for participants older than 65 years, RR (95% CI) were 1.93 (1.65-2.22) (I2 = 0.0%, p=0.808) for all-cause mortality. Conclusion: Available observational evidence shows that unintentional weight loss significantly impacted on all-cause mortality in primary prevention cohorts, specially in aged populations. These findings should be accounted for when discussing the obesity paradox in general population.