Examine the impact of rest days on musculoskeletal (MSK) injury incidence in Major League Baseball (MLB) starting pitchers. Descriptive epidemiological study. MLB pitching and injury reports. PARTICIPANTS: MLB starting pitchers. Data (2022-2023) were obtained from Baseball-Reference.com and fangraphs.com. Teams were grouped by average rest days between starts (Group A <5 rest days, Group B >5 rest days). Poisson regression was used to compare main outcome measure incidence rate ratios (IRRs). Number of rest days between starts. Pitches per start, MSK injury incidence, injured list (IL) days for MSK injury. From 2022 to 2023, the average MLB rest days between starts was 4.80. Group A had 54 teams. Group B had 6 teams. The range of average rest days per start by team was 4.56 to 5.73 with a mean of 4.80. Group B pitchers spent 10.7 days on IL for MSK injuries per 1000 pitches, while Group A spent 13.6 days on IL (IRR = 0.78 [95% CI, 0.72-0.85]; P < 0.0001). Group B averaged 0.93 more pitches per start than Group A (P = 0.0164). Group B had a lower number of IL assignments for MSK injuries per 1000 pitches (0.245 vs 0.351, IRR = 0.70 [95% CI, 0.38-1.18]; P = 0.1715). Starting pitchers on MLB teams averaging > 5 rest days between starts spent less time on the IL for MSK injuries than MLB teams averaging < 5 rest days from 2022 to 2023. There was no clinically significant difference in pitch count and no significant difference in the number of IL assignments for MSK injuries.