Hydrogel spacers are a tool to improve dosimetry and overall quality of life with limited follow-up in men receiving radiotherapy for prostate cancer. This study is a pooled analysis of prospective cohorts with long-term quality of life (QOL) follow-up with or without a rectal spacer to minimize dose to rectum as well as other adjacent organs at risk. QOL was examined using the Expanded Prostate Cancer Index Composite (EPIC) and mean changes from baseline to EPIC domains were evaluated. A total of 126 patients with good pre-treatment sexual function (baseline EPIC >/=60) including 88 patients from a randomized multi-institutional trial of radiation with or without hydrogel rectal spacer with a QOL end-point were pooled with 38 non-randomized patients from a single institution with prospective QOL collection in patients with or without hydrogel spacer. The proportions of men with a predetermined minimally important differences (MIDs) relative to pre-treatment baseline (11 point decline from baseline = MIDx1 and 22 point decline from baseline = MIDx2) in sexual function were evaluated. A total of 126 men were evaluated (64% with spacer and 36% without) with QOL data being available for 68 men beyond 24 months of follow-up (median: 33 months, range: 2.5-69.4 months). MID was more common in men without a rectal spacer at 15 months (60.5% vs 44.4%) and at >/= 24 months (80% vs 55%). MIDX2 occurred at 15 months of 45% in men without rectal spacer vs 29% in men with rectal spacer and >/= 24months in 68% of men without rectal spacer vs 39% with rectal spacer. At >/= 24 months of follow up, men without spacer were more likely to have 1xMID in sexual QOL (11 point decline, p= 0.041, Fisher Exact) as well as 2xMID (22 point decline, p=0.025, Fischer Exact) declines. The use of rectal separation was associated with adequate erectile quality. In men with rectal spacer at late follow up, 63% of patients had firm enough erections for intercourse and 1% had no erectile function compared to 28% adequate erectile function for intercourse and 12% without any erectile function in patients without rectal spacer. In this pooled analysis of QOL after prostate radiotherapy with up to 5-years of follow-up, utilization of a hydrogel rectal spacer was associated with less MID per patient reported sexual QOL. This was especially important in patient reported adequate erectile function for intercourse.